Delivery Of Biological Compounds To Ischemic And/Or Infarcted Tissue

ABSTRACT

The delivery of biological compounds to ischemic and/or infarcted tissue are described herein where such a system may include a deployment catheter and an attached imaging hood deployable into an expanded configuration. In use, the imaging hood is placed against or adjacent to a region of tissue to be imaged in a body lumen that is normally filled with an opaque bodily fluid such as blood. A translucent or transparent fluid, such as saline, can be pumped into the imaging hood until the fluid displaces any blood, thereby leaving a clear region of tissue to be imaged via an imaging element in the deployment catheter. Additionally, any number of therapeutic tools can also be passed through the deployment catheter and into the imaging hood for performing any number of procedures on the tissue for identifying, locating, and/or accessing ischemic and/or infarcted tissue.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/828,267, filed Jul. 25, 2007, which claims the benefit of U.S.Provisional Application No. 60/821,117 filed Aug. 1, 2006. U.S. patentapplication Ser. No. 11/828,267 is a continuation-in-part of U.S. patentapplication Ser. No. 11/259,498 (now U.S. Pat. No. 7,860,555), whichclaims the benefit of U.S. Provisional Application No. 60/649,246, filedon Feb. 2, 2005, each of which is incorporated herein by reference inits entirety.

FIELD OF THE INVENTION

The present invention relates generally to medical devices used foraccessing, visualizing, and/or treating regions of tissue within a body.More particularly, the present invention relates to methods andapparatus for locating and accessing ischemic and/or infracted tissueand for treating the tissue by delivering biologically active compoundswithin a patient heart.

BACKGROUND OF THE INVENTION

Conventional devices for accessing and visualizing interior regions of abody lumen are known. For example, ultrasound devices have been used toproduce images from within a body in vivo. Ultrasound has been used bothwith and without contrast agents, which typically enhanceultrasound-derived images.

Other conventional methods have utilized catheters or probes havingposition sensors deployed within the body lumen, such as the interior ofa cardiac chamber. These types of positional sensors are typically usedto determine the movement of a cardiac tissue surface or the electricalactivity within the cardiac tissue. When a sufficient number of pointshave been sampled by the sensors, a “map” of the cardiac tissue may begenerated.

Another conventional device utilizes an inflatable balloon which istypically introduced intravascularly in a deflated state and theninflated against the tissue region to be examined. Imaging is typicallyaccomplished by an optical fiber or other apparatus such as electronicchips for viewing the tissue through the membrane(s) of the inflatedballoon. Moreover, the balloon must generally be inflated for imaging.Other conventional balloons utilize a cavity or depression formed at adistal end of the inflated balloon. This cavity or depression is pressedagainst the tissue to be examined and is flushed with a clear fluid toprovide a clear pathway through the blood.

However, such imaging balloons have many inherent disadvantages. Forinstance, such balloons generally require that the balloon be inflatedto a relatively large size which may undesirably displace surroundingtissue and interfere with fine positioning of the imaging system againstthe tissue. Moreover, the working area created by such inflatableballoons are generally cramped and limited in size. Furthermore,inflated balloons may be susceptible to pressure changes in thesurrounding fluid. For example, if the environment surrounding theinflated balloon undergoes pressure changes, e.g., during systolic anddiastolic pressure cycles in a beating heart, the constant pressurechange may affect the inflated balloon volume and its positioning toproduce unsteady or undesirable conditions for optimal tissue imaging.

Accordingly, these types of imaging modalities are generally unable toprovide desirable images useful for sufficient diagnosis and therapy ofthe endoluminal structure, due in part to factors such as dynamic forcesgenerated by the natural movement of the heart. Moreover, anatomicstructures within the body can occlude or obstruct the image acquisitionprocess. Also, the presence and movement of opaque bodily fluids such asblood generally make in vivo imaging of tissue regions within the heartdifficult.

Other external imaging modalities are also conventionally utilized. Forexample, computed tomography (CT) and magnetic resonance imaging (MRI)are typical modalities which are widely used to obtain images of bodylumens such as the interior chambers of the heart. However, such imagingmodalities fail to provide real-time imaging for intra-operativetherapeutic procedures. Fluoroscopic imaging, for instance, is widelyused to identify anatomic landmarks within the heart and other regionsof the body. However, fluoroscopy fails to provide an accurate image ofthe tissue quality or surface and also fails to provide forinstrumentation for performing tissue manipulation or other therapeuticprocedures upon the visualized tissue regions. In addition, fluoroscopyprovides a shadow of the intervening tissue onto a plate or sensor whenit may be desirable to view the intraluminal surface of the tissue todiagnose pathologies or to perform some form of therapy on it.

Thus, a tissue imaging system which is able to provide real-time in vivoaccess to and images of tissue regions within body lumens such as theheart through opaque media such as blood and which also provideinstruments for therapeutic procedures upon the visualized tissue aredesirable.

SUMMARY OF THE INVENTION

A tissue imaging and manipulation apparatus that may be utilized forprocedures within a body lumen, such as the heart, in whichvisualization of the surrounding tissue is made difficult, if notimpossible, by medium contained within the lumen such as blood, isdescribed below. Generally, such a tissue imaging and manipulationapparatus comprises an optional delivery catheter or sheath throughwhich a deployment catheter and imaging hood may be advanced forplacement against or adjacent to the tissue to be imaged.

The deployment catheter may define a fluid delivery lumen therethroughas well as an imaging lumen within which an optical imaging fiber orassembly may be disposed for imaging tissue. When deployed, the imaginghood may be expanded into any number of shapes, e.g., cylindrical,conical as shown, semi-spherical, etc., provided that an open area orfield is defined by the imaging hood. The open area is the area withinwhich the tissue region of interest may be imaged. The imaging hood mayalso define an atraumatic contact lip or edge for placement or abutmentagainst the tissue region of interest. Moreover, the distal end of thedeployment catheter or separate manipulatable catheters may bearticulated through various controlling mechanisms such as push-pullwires manually or via computer control

In operation, after the imaging hood has been deployed, fluid may bepumped at a positive pressure through the fluid delivery lumen until thefluid fills the open area completely and displaces any blood from withinthe open area. The fluid may comprise any biocompatible fluid, e.g.,saline, water, plasma, Fluorinert™, etc., which is sufficientlytransparent to allow for relatively undistorted visualization throughthe fluid. The fluid may be pumped continuously or intermittently toallow for image capture by an optional processor which may be incommunication with the assembly.

One particular application for the tissue visualization system includesutilizing the system for detecting the presence and/or location ofischemic and/or infarcted tissue by visual inspection and/or measurementof one or more parameter of the tissue. Any number of physiologicparameters can be utilized to obtain measurements of the visualizedtissue to detect the certain parameters, e.g., partial pressure valuesof oxygen (PO2) and carbon dioxide (PCO2); temperature differencesbetween tissue regions; biomarkers indicative of injured tissue;electrical current and/or electrical potential differences through thetissue; variations in tissue surface hardness and deflection betweentissue regions; etc.

Once the injured tissue region has been identified, a number oftreatments may be utilized for injecting or infusing bioactive agentsinto or upon the tissue. Accordingly, a number of systems and methodsfor utilizing instruments to locate and/or access ischemic and/orinfarcted tissue and to treat the tissue by delivering biologicallyactive compounds may be utilized.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1A shows a side view of one variation of a tissue imaging apparatusduring deployment from a sheath or delivery catheter.

FIG. 1B shows the deployed tissue imaging apparatus of FIG. 1A having anoptionally expandable hood or sheath attached to an imaging and/ordiagnostic catheter.

FIG. 1C shows an end view of a deployed imaging apparatus.

FIGS. 1D to 1F show the apparatus of FIGS. 1A to 1C with an additionallumen, e.g., for passage of a guidewire therethrough.

FIGS. 2A and 2B show one example of a deployed tissue imager positionedagainst or adjacent to the tissue to be imaged and a flow of fluid, suchas saline, displacing blood from within the expandable hood.

FIG. 3A shows an articulatable imaging assembly which may be manipulatedvia push-pull wires or by computer control.

FIGS. 3B and 3C show steerable instruments, respectively, where anarticulatable delivery catheter may be steered within the imaging hoodor a distal portion of the deployment catheter itself may be steered.

FIGS. 4A to 4C show side and cross-sectional end views, respectively, ofanother variation having an off-axis imaging capability.

FIGS. 5A and 5B show examples of various visualization imagers which maybe utilized within or along the imaging hood.

FIGS. 6A to 6C illustrate deployment catheters having one or moreoptional inflatable balloons or anchors for stabilizing the deviceduring a procedure.

FIGS. 7A and 7B illustrate a variation of an anchoring mechanism such asa helical tissue piercing device for temporarily stabilizing the imaginghood relative to a tissue surface.

FIG. 7C shows another variation for anchoring the imaging hood havingone or more tubular support members integrated with the imaging hood;each support members may define a lumen therethrough for advancing ahelical tissue anchor within.

FIG. 8A shows an illustrative example of one variation of how a tissueimager may be utilized with an imaging device.

FIG. 8B shows a further illustration of a hand-held variation of thefluid delivery and tissue manipulation system.

FIGS. 9A to 9C illustrate an example of capturing several images of thetissue at multiple regions.

FIG. 10 shows a perspective view of the tissue visualization cathetervisualizing the underlying tissue for the presence of ischemic and/orinfarcted tissue.

FIGS. 11A and 11B show side and perspective views, respectively, of avariation of the tissue visualization catheter having a needle catheterfor injecting a fluorescent dye into the underlying tissue to determinewhether ischemic and/or infarcted tissue is present.

FIG. 12 shows a perspective view of a variation of the tissuevisualization catheter having a single probe configured to obtainmeasurements of a variety of physiologic parameters for determining thepresence and/or location of ischemic and/or infarcted tissue.

FIG. 13 shows a perspective view of another variation of the tissuevisualization catheter having a multi-probe configuration to obtainmeasurements of a variety of physiologic parameters for determiningpresence and location of ischemic and/or infarcted tissue.

FIG. 14A shows a perspective view of a helical needle having a pluralityof holes or openings along a surface of the needle body for delivery ofbioactive substances into tissue

FIG. 14B shows a perspective view of the helical delivery needle to beadvanced into the underlying tissue while under direct visualization.

FIG. 15 shows a perspective view of another variation of thevisualization catheter having multiple helical delivery needlespositioned circumferentially around a periphery of the hood.

FIGS. 16A and 16B illustrate perspective views of another variationwhere a laser probe, e.g., an optical fiber bundle coupled to a lasergenerator, may be inserted through the work channel of the tissuevisualization catheter and activated for ablation treatment prior todelivery of bioactive substances into the ablated tissue.

FIG. 17 shows a cross sectional view of the heart illustrating theimplantation of a deposited delivery of a bioactive substance, e.g., inthe anterolateral myocardium of the left ventricle.

DETAILED DESCRIPTION OF THE INVENTION

A tissue-imaging and manipulation apparatus described below is able toprovide real-time images in vivo of tissue regions within a body lumensuch as a heart, which is filled with blood flowing dynamicallytherethrough and is also able to provide intravascular tools andinstruments for performing various procedures upon the imaged tissueregions. Such an apparatus may be utilized for many procedures, e.g.,facilitating trans-septal access to the left atrium, cannulating thecoronary sinus, diagnosis of valve regurgitation/stenosis,valvuloplasty, atrial appendage closure, arrhythmogenic focus ablation,among other procedures. Details of tissue imaging and manipulationsystems and methods which may be utilized with apparatus and methodsdescribed herein are described in U.S. patent application Ser. No.11/259,498 filed Oct. 25, 2005 (U.S. Pat. Pub. No. 2006/0184048 A1),which is incorporated herein by reference in its entirety.

One variation of a tissue access and imaging apparatus is shown in thedetail perspective views of FIGS. 1A to 1C. As shown in FIG. 1A, tissueimaging and manipulation assembly 10 may be delivered intravascularlythrough the patient's body in a low-profile configuration via a deliverycatheter or sheath 14. In the case of treating tissue, such as themitral valve located at the outflow tract of the left atrium of theheart, it is generally desirable to enter or access the left atriumwhile minimizing trauma to the patient. To non-operatively effect suchaccess, one conventional approach involves puncturing the intra-atrialseptum from the right atrial chamber to the left atrial chamber in aprocedure commonly called a trans-septal procedure or septostomy. Forprocedures such as percutaneous valve repair and replacement,trans-septal access to the left atrial chamber of the heart may allowfor larger devices to be introduced into the venous system than cangenerally be introduced percutaneously into the arterial system.

When the imaging and manipulation assembly 10 is ready to be utilizedfor imaging tissue, imaging hood 12 may be advanced relative to catheter14 and deployed from a distal opening of catheter 14, as shown by thearrow. Upon deployment, imaging hood 12 may be unconstrained to expandor open into a deployed imaging configuration or may form anon-inflatable barrier or membrane, as shown in FIG. 1B. Imaging hood 12may be fabricated from a variety of pliable or conformable biocompatiblematerial including but not limited to, e.g., polymeric, plastic, orwoven materials. One example of a woven material is Kevlar® (E. I. duPont de Nemours, Wilmington, Del.), which is an aramid and which can bemade into thin, e.g., less than 0.001 in., materials which maintainenough integrity for such applications described herein. Moreover, theimaging hood 12 may be fabricated from a translucent or opaque materialand in a variety of different colors to optimize or attenuate anyreflected lighting from surrounding fluids or structures, i.e.,anatomical or mechanical structures or instruments. In either case,imaging hood 12 may be fabricated into a uniform structure or ascaffold-supported structure, in which case a scaffold made of a shapememory alloy, such as Nitinol, or a spring steel, or plastic, etc., maybe fabricated and covered with the polymeric, plastic, or wovenmaterial.

Imaging hood 12 may be attached at interface 24 to a deployment catheter16 which may be translated independently of deployment catheter orsheath 14. Attachment of interface 24 may be accomplished through anynumber of conventional methods. Deployment catheter 16 may define afluid delivery lumen 18 as well as an imaging lumen 20 within which anoptical imaging fiber or assembly may be disposed for imaging tissue.When deployed, imaging hood 12 may expand into any number of shapes,e.g., cylindrical, conical as shown, semi-spherical, etc., provided thatan open area or field 26 is defined by imaging hood 12. The open area 26is the area within which the tissue region of interest may be imaged.Imaging hood 12 may also define an atraumatic contact lip or edge 22 forplacement or abutment against the tissue region of interest. Moreover,the diameter of imaging hood 12 at its maximum fully deployed diameter,e.g., at contact lip or edge 22, is typically greater relative to adiameter of the deployment catheter 16 (although a diameter of contactlip or edge 22 may be made to have a smaller or equal diameter ofdeployment catheter 16). For instance, the contact edge diameter mayrange anywhere from 1 to 5 times (or even greater, as practicable) adiameter of deployment catheter 16. FIG. 1C shows an end view of theimaging hood 12 in its deployed configuration. Also shown are thecontact lip or edge 22 and fluid delivery lumen 18 and imaging lumen 20.

The imaging and manipulation assembly 10 may additionally define aguidewire lumen therethrough, e.g., a concentric or eccentric lumen, asshown in the side and end views, respectively, of FIGS. 1D to 1F. Thedeployment catheter 16 may define guidewire lumen 19 for facilitatingthe passage of the system over or along a guidewire 17, which may beadvanced intravascularly within a body lumen. The deployment catheter 16may then be advanced over the guidewire 17, as generally known in theart.

In operation, after imaging hood 12 has been deployed, as in FIG. 1B,and desirably positioned against the tissue region to be imaged alongcontact edge 22, the displacing fluid may be pumped at positive pressurethrough fluid delivery lumen 18 until the fluid fills open area 26completely and displaces any fluid 28 from within open area 26. Thedisplacing fluid flow may be laminarized to improve its clearing effectand to help prevent blood from re-entering the imaging hood 12.Alternatively, fluid flow may be started before the deployment takesplace. The displacing fluid, also described herein as imaging fluid, maycomprise any biocompatible fluid, e.g., saline, water, plasma, etc.,which is sufficiently transparent to allow for relatively undistortedvisualization through the fluid. Alternatively or additionally, anynumber of therapeutic drugs may be suspended within the fluid or maycomprise the fluid itself which is pumped into open area 26 and which issubsequently passed into and through the heart and the patient body.

As seen in the example of FIGS. 2A and 2B, deployment catheter 16 may bemanipulated to position deployed imaging hood 12 against or near theunderlying tissue region of interest to be imaged, in this example aportion of annulus A of mitral valve MY within the left atrial chamber.As the surrounding blood 30 flows around imaging hood 12 and within openarea 26 defined within imaging hood 12, as seen in FIG. 2A, theunderlying annulus A is obstructed by the opaque blood 30 and isdifficult to view through the imaging lumen 20. The translucent fluid28, such as saline, may then be pumped through fluid delivery lumen 18,intermittently or continuously, until the blood 30 is at leastpartially, and preferably completely, displaced from within open area 26by fluid 28, as shown in FIG. 2B.

Although contact edge 22 need not directly contact the underlyingtissue, it is at least preferably brought into close proximity to thetissue such that the flow of clear fluid 28 from open area 26 may bemaintained to inhibit significant backflow of blood 30 back into openarea 26. Contact edge 22 may also be made of a soft elastomeric materialsuch as certain soft grades of silicone or polyurethane, as typicallyknown, to help contact edge 22 conform to an uneven or rough underlyinganatomical tissue surface. Once the blood 30 has been displaced fromimaging hood 12, an image may then be viewed of the underlying tissuethrough the clear fluid 30. This image may then be recorded or availablefor real-time viewing for performing a therapeutic procedure. Thepositive flow of fluid 28 may be maintained continuously to provide forclear viewing of the underlying tissue. Alternatively, the fluid 28 maybe pumped temporarily or sporadically only until a clear view of thetissue is available to be imaged and recorded, at which point the fluidflow 28 may cease and blood 30 may be allowed to seep or flow back intoimaging hood 12. This process may be repeated a number of times at thesame tissue region or at multiple tissue regions.

In desirably positioning the assembly at various regions within thepatient body, a number of articulation and manipulation controls may beutilized. For example, as shown in the articulatable imaging assembly 40in FIG. 3A, one or more push-pull wires 42 may be routed throughdeployment catheter 16 for steering the distal end portion of the devicein various directions 46 to desirably position the imaging hood 12adjacent to a region of tissue to be visualized. Depending upon thepositioning and the number of push-pull wires 42 utilized, deploymentcatheter 16 and imaging hood 12 may be articulated into any number ofconfigurations 44. The push-pull wire or wires 42 may be articulated viatheir proximal ends from outside the patient body manually utilizing oneor more controls. Alternatively, deployment catheter 16 may bearticulated by computer control, as further described below.

Additionally or alternatively, an articulatable delivery catheter 48,which may be articulated via one or more push-pull wires and having animaging lumen and one or more working lumens, may be delivered throughthe deployment catheter 16 and into imaging hood 12. With a distalportion of articulatable delivery catheter 48 within imaging hood 12,the clear displacing fluid may be pumped through delivery catheter 48 ordeployment catheter 16 to clear the field within imaging hood 12. Asshown in FIG. 3B, the articulatable delivery catheter 48 may bearticulated within the imaging hood to obtain a better image of tissueadjacent to the imaging hood 12. Moreover, articulatable deliveycatheter 48 may be articulated to direct an instrument or tool passedthrough the catheter 48, as described in detail below, to specific areasof tissue imaged through imaging hood 12 without having to repositiondeployment catheter 16 and re-clear the imaging field within hood 12.

Alternatively, rather than passing an articulatable delivery catheter 48through the deployment catheter 16, a distal portion of the deploymentcatheter 16 itself may comprise a distal end 49 which is articulatablewithin imaging hood 12, as shown in FIG. 3C. Directed imaging,instrument delivery, etc., may be accomplished directly through one ormore lumens within deployment catheter 16 to specific regions of theunderlying tissue imaged within imaging hood 12.

Visualization within the imaging hood 12 may be accomplished through animaging lumen 20 defined through deployment catheter 16, as describedabove. In such a configuration, visualization is available in astraight-line manner, i.e., images are generated from the field distallyalong a longitudinal axis defined by the deployment catheter 16.Alternatively or additionally, an articulatable imaging assembly havinga pivotable support member 50 may be connected to, mounted to, orotherwise passed through deployment catheter 16 to provide forvisualization off-axis relative to the longitudinal axis defined bydeployment catheter 16, as shown in FIG. 4A. Support member 50 may havean imaging element 52, e.g., a CCD or CMOS imager or optical fiber,attached at its distal end with its proximal end connected to deploymentcatheter 16 via a pivoting connection 54.

If one or more optical fibers are utilized for imaging, the opticalfibers 58 may be passed through deployment catheter 16, as shown in thecross-section of FIG. 4B, and routed through the support member 50. Theuse of optical fibers 58 may provide for increased diameter sizes of theone or several lumens 56 through deployment catheter 16 for the passageof diagnostic and/or therapeutic tools therethrough. Alternatively,electronic chips, such as a charge coupled device (CCD) or a CMOSimager, which are typically known, may be utilized in place of theoptical fibers 58, in which case the electronic imager may be positionedin the distal portion of the deployment catheter 16 with electric wiresbeing routed proximally through the deployment catheter 16.Alternatively, the electronic imagers may be wirelessly coupled to areceiver for the wireless transmission of images. Additional opticalfibers or light emitting diodes (LEDs) can be used to provide lightingfor the image or operative theater, as described below in furtherdetail. Support member 50 may be pivoted via connection 54 such that themember 50 can be positioned in a low-profile configuration withinchannel or groove 60 defined in a distal portion of catheter 16, asshown in the cross-section of FIG. 4C. During intravascular delivery ofdeployment catheter 16 through the patient body, support member 50 canbe positioned within channel or groove 60 with imaging hood 12 also inits low-profile configuration. During visualization, imaging hood 12 maybe expanded into its deployed configuration and support member 50 may bedeployed into its off-axis configuration for imaging the tissue adjacentto hood 12, as in FIG. 4A. Other configurations for support member 50for oil-axis visualization may be utilized, as desired.

FIG. 5A shows a partial cross-sectional view of an example where one ormore optical fiber bundles 62 may be positioned within the catheter andwithin imaging hood 12 to provide direct in-line imaging of the openarea within hood 12. FIG. 5B shows another example where an imagingelement 64 (e.g., CCD or CMOS electronic imager) may be placed along aninterior surface of imaging hood 12 to provide imaging of the open areasuch that the imaging element 64 is off-axis relative to a longitudinalaxis of the hood 12. The off-axis position of element 64 may provide fordirect visualization and uninhibited access by instruments from thecatheter to the underlying tissue during treatment.

To facilitate stabilization of the deployment catheter 16 during aprocedure, one or more inflatable balloons or anchors 76 may bepositioned along the length of catheter 16, as shown in FIG. 6A. Forexample, when utilizing a trans-septal approach across the atrial septumAS into the left atrium LA, the inflatable balloons 76 may be inflatedfrom a low-profile into their expanded configuration to temporarilyanchor or stabilize the catheter 16 position relative to the heart H.FIG. 6B shows a first balloon 78 inflated while FIG. 6C also shows asecond balloon 80 inflated proximal to the first balloon 78. In such aconfiguration, the septal wall AS may be wedged or sandwiched betweenthe balloons 78, 80 to temporarily stabilize the catheter 16 and imaginghood 12. A single balloon 78 or both balloons 78, 80 may be used. Otheralternatives may utilize expandable mesh members, malecots, or any othertemporary expandable structure. After a procedure has been accomplished,the balloon assembly 76 may be deflated or re-configured into alow-profile for removal of the deployment catheter 16.

To further stabilize a position of the imaging hood 12 relative to atissue surface to be imaged, various anchoring mechanisms may beoptionally employed for temporarily holding the imaging hood 12 againstthe tissue. Such anchoring mechanisms may be particularly useful forimaging tissue which is subject to movement, e.g., when imaging tissuewithin the chambers of a beating heart. A tool delivery catheter 82having at least one instrument lumen and an optional visualization lumenmay be delivered through deployment catheter 16 and into an expandedimaging hood 12. As the imaging hood 12 is brought into contact againsta tissue surface T to be examined, an anchoring mechanisms such as ahelical tissue piercing device 84 may be passed through the tooldelivery catheter 82, as shown in FIG. 7A, and into imaging hood 12.

The helical tissue engaging device 84 may be torqued from its proximalend outside the patient body to temporarily anchor itself into theunderlying tissue surface T. Once embedded within the tissue T, thehelical tissue engaging device 84 may be pulled proximally relative todeployment catheter 16 while the deployment catheter 16 and imaging hood12 are pushed distally, as indicated by the arrows in FIG. 7B, to gentlyforce the contact edge or lip 22 of imaging hood against the tissue T.The positioning of the tissue engaging device 84 may be lockedtemporarily relative to the deployment catheter 16 to ensure securepositioning of the imaging hood 12 during a diagnostic or therapeuticprocedure within the imaging hood 12. After a procedure, tissue engagingdevice 84 may be disengaged from the tissue by torquing its proximal endin the opposite direction to remove the anchor form the tissue T and thedeployment catheter 16 may be repositioned to another region of tissuewhere the anchoring process may be repeated or removed from the patientbody. The tissue engaging device 84 may also be constructed from otherknown tissue engaging devices such as vacuum-assisted engagement orgrasper-assisted engagement tools, among others.

Although a helical anchor 84 is shown, this is intended to beillustrative and other types of temporary anchors may be utilized, e.g.,hooked or barbed anchors, graspers, etc. Moreover, the tool deliverycatheter 82 may be omitted entirely and the anchoring device may bedelivered directly through a lumen defined through the deploymentcatheter 16.

In another variation where the tool delivery catheter 82 may be omittedentirely to temporarily anchor imaging hood 12, FIG. 7C shows an imaginghood 12 having one or more tubular support members 86, e.g., foursupport members 86 as shown, integrated with the imaging hood 12. Thetubular support members 86 may define lumens therethrough each havinghelical tissue engaging devices 88 positioned within. When an expandedimaging hood 12 is to be temporarily anchored to the tissue, the helicaltissue engaging devices 88 may be urged distally to extend from imaginghood 12 and each may be torqued from its proximal end to engage theunderlying tissue T. Each of the helical tissue engaging devices 88 maybe advanced through the length of deployment catheter 16 or they may bepositioned within tubular support members 86 during the delivery anddeployment of imaging hood 12. Once the procedure within imaging hood 12is finished, each of the tissue engaging devices 88 may be disengagedfrom the tissue and the imaging hood 12 may be repositioned to anotherregion of tissue or removed from the patient body.

An illustrative example is shown in FIG. 8A of a tissue imaging assemblyconnected to a fluid delivery system 90 and to an optional processor 98and image recorder and/or viewer 100. The fluid delivery system 90 maygenerally comprise a pump 92 and an optional valve 94 for controllingthe flow rate of the fluid into the system. A fluid reservoir 96,fluidly connected to pump 92, may hold the fluid to be pumped throughimaging hood 12. An optional central processing unit or processor 98 maybe in electrical communication with fluid delivery system 90 forcontrolling flow parameters such as the flow rate and/or velocity of thepumped fluid. The processor 98 may also be in electrical communicationwith an image recorder and/or viewer 100 for directly viewing the imagesof tissue received from within imaging hood 12. Imager recorder and/orviewer 100 may also be used not only to record the image but also thelocation of the viewed tissue region, if so desired.

Optionally, processor 98 may also be utilized to coordinate the fluidflow and the image capture. For instance, processor 98 may be programmedto provide for fluid flow from reservoir 96 until the tissue area hasbeen displaced of blood to obtain a clear image. Once the image has beendetermined to be sufficiently clear, either visually by a practitioneror by computer, an image of the tissue may be captured automatically byrecorder 100 and pump 92 may be automatically stopped or slowed byprocessor 98 to cease the fluid flow into the patient. Other variationsfor fluid delivery and image capture are, of course, possible and theaforementioned configuration is intended only to be illustrative and notlimiting.

FIG. 8B shows a further illustration of a hand-held variation of thefluid delivery and tissue manipulation system 110. In this variation,system 110 may have a housing or handle assembly 112 which can be heldor manipulated by the physician from outside the patient body. The fluidreservoir 114, shown in this variation as a syringe, can be fluidlycoupled to the handle assembly 112 and actuated via a pumping mechanism116, e.g., lead screw. Fluid reservoir 114 may be a simple reservoirseparated from the handle assembly 112 and fluidly coupled to handleassembly 112 via one or more tubes. The fluid flow rate and othermechanisms may be metered by the electronic controller 118.

Deployment of imaging hood 12 may be actuated by a hood deploymentswitch 120 located on the handle assembly 112 while dispensation of thefluid from reservoir 114 may be actuated by a fluid deployment switch122, which can be electrically coupled to the controller 118. Controller118 may also be electrically coupled to a wired or wireless antenna 124optionally integrated with the handle assembly 112, as shown in thefigure. The wireless antenna 124 can be used to wirelessly transmitimages captured from the imaging hood 12 to a receiver, e.g., viaBluetooth® wireless technology (Bluetooth SIG, Inc., Bellevue, Wash.),RF, etc., for viewing on a monitor 128 or for recording for laterviewing.

Articulation control of the deployment catheter 16, or a deliverycatheter or sheath 14 through which the deployment catheter 16 may bedelivered, may be accomplished by computer control, as described above,in which case an additional controller may be utilized with handleassembly 112. In the case of manual articulation, handle assembly 112may incorporate one or more articulation controls 126 for manualmanipulation of the position of deployment catheter 16. Handle assembly112 may also define one or more instrument ports 130 through which anumber of intravascular tools may be passed for tissue manipulation andtreatment within imaging hood 12, as described further below.Furthermore, in certain procedures, fluid or debris may be sucked intoimaging hood 12 for evacuation from the patient body by optionallyfluidly coupling a suction pump 132 to handle assembly 112 or directlyto deployment catheter 16.

As described above, fluid may be pumped continuously into imaging hood12 to provide for clear viewing of the underlying tissue. Alternatively,fluid may be pumped temporarily or sporadically only until a clear viewof the tissue is available to be imaged and recorded, at which point thefluid flow may cease and the blood may be allowed to seep or flow backinto imaging hood 12. FIGS. 9A to 9C illustrate an example of capturingseveral images of the tissue at multiple regions. Deployment catheter 16may be desirably positioned and imaging hood 12 deployed and broughtinto position against a region of tissue to be imaged, in this examplethe tissue surrounding a mitral valve MV within the left atrium of apatient's heart. The imaging hood 12 may be optionally anchored to thetissue, as described above, and then cleared by pumping the imagingfluid into the hood 12. Once sufficiently clear, the tissue may bevisualized and the image captured by control electronics 118. The firstcaptured image 140 may be stored and/or transmitted wirelessly 124 to amonitor 128 for viewing by the physician, as shown in FIG. 9A.

The deployment catheter 16 may be then repositioned to an adjacentportion of mitral valve MV, as shown in FIG. 9B, where the process maybe repeated to capture a second image 142 for viewing and/or recording.The deployment catheter 16 may again be repositioned to another regionof tissue, as shown in FIG. 9C, where a third image 144 may be capturedfor viewing and/or recording. This procedure may be repeated as manytimes as necessary for capturing a comprehensive image of the tissuesurrounding mitral valve MV, or any other tissue region. When thedeployment catheter 16 and imaging hood 12 is repositioned from tissueregion to tissue region, the pump may be stopped during positioning andblood or surrounding fluid may be allowed to enter within imaging hood12 until the tissue is to be imaged, where the imaging hood 12 may becleared, as above.

As mentioned above, when the imaging hood 12 is cleared by pumping theimaging fluid within for clearing the blood or other bodily fluid, thefluid may be pumped continuously to maintain the imaging fluid withinthe hood 12 at a positive pressure or it may be pumped under computercontrol for slowing or stopping the fluid flow into the hood 12 upondetection of various parameters or until a clear image of the underlyingtissue is obtained. The control electronics 118 may also be programmedto coordinate the fluid flow into the imaging hood 12 with variousphysical parameters to maintain a clear image within imaging hood 12.

Detail examples and descriptions of a visualization catheter device andsystem which may be utilized herein are shown and described in furtherdetail in U.S. patent application Ser. No. 11/259,498 filed Oct. 25,2005, which has been incorporated herein above in its entirety.

One particular application for the tissue visualization system includesutilizing the system for detecting the presence and/or location ofischemic and/or infarcted tissue by visual inspection and/or measurementof one or more parameter of the tissue. Any number of physiologicparameters can be utilized to obtain measurements of the visualizedtissue to detect the certain parameters, e.g., partial pressure valuesof oxygen (PO2) and carbon dioxide (PCO2); temperature differencesbetween tissue regions; biomarkers indicative of injured tissue;electrical current and/or electrical potential differences through thetissue; variations in tissue surface hardness and deflection betweentissue regions; etc.

One method for detecting the ischemic and/or infarcted tissue is byvisual inspection alone. As shown in the perspective view of FIG. 10,with hood 12 placed over a tissue region T to be inspected, transparentdisplacement fluid 150 may be infused into the hood 12 and theunderlying tissue may be visually inspected via imaging element 64. Indetermining the presence and/or location of the affected tissue, theuser may directly visualize the tissue surface via the visualizationcatheter and ascertain, e.g., the colors, intensities, and patterns ofappearance. Accordingly, regions of healthy and diseased tissue may beidentified. Such physical parameters are generally known to one of skillin the art as indicated in various clinical-pathologic correlationstudies.

Another method for detecting certain tissue conditions may incorporatethe use of fluorescent compounds injected into the tissue being visuallyinspected to enhance any contrasts in the tissue appearance. As shown inthe respective side and perspective views of FIGS. 11A and 11B, withhood 12 placed against the tissue region T to be inspected and the hoodopen area purged of blood, hollow piercing needle 160 may be advancedthrough deployment catheter 16 and into the underlying tissue T topenetrate at least partially into the tissue to directly administer afluorescent chemical dye, e.g., indocyanin green. Alternatively,piercing needle 160 may be advanced against the tissue surface andsimply drip the fluorescent dye onto or over the tissue surface. In yetanother alternative, the fluorescent chemical dye may be systemicallyadministered to the patient via an intravenous route. When thefluorescent dye has been absorbed by the tissue region T to beinspected, the tissue may exhibit a visual appearance which isindicative of certain physiological characteristics. For instance, thedyed tissue region may exhibit different patterns of variouslyfluorescing regions of tissue which may be indicative of tissue health,e.g., healthy, perfused tissue; ischemic tissue; infarcted tissue,necrotic tissue, etc.

The intensity and pattern of fluorescence may be observed directly bythe user without image processing. Alternatively, imaging element 64(which may be optionally filtered) may be in communication with signalprocessor 162 which may take the images and process them for analysis ofthe emitted wavelength distribution. The emitted wavelength distributionmay be correlated to determine the physiologic characteristics of thetissue and the resulting image may be displayed upon a monitor 164 foruser evaluation.

Another variation for determining tissue condition may include the useof a sensor probe 170 advanced into contact against the tissue surface Twhile under visualization from imaging element 64, as shown in FIG. 12.Sensor probe 170 may be used to measure physiologic data such as localtissue concentrations of the partial pressure values of oxygen (PO2)and/or carbon dioxide (PCO2) within the tissue region T. This data maybe analyzed by processor 162 to extrapolate the locations of tissuehaving relatively higher PO2 values and/or lower PCO2 values which areindicative of well-perfused (and healthy) tissue. Conversely, regionswith relatively lower PO2 and/or higher PCO2 values may indicatepoorly-perfused and presumably ischemic and/or infarcted tissue. Themeasured concentration values of PO2 and/or PCO2 may be processed 162for visual representation 164 to and evaluation by the user, asillustrated by the concentration profile 172 as measured by probe 170.

Aside from PO2 and PCO2 concentration measurement, sensor probe 170 maybe additionally or alternatively configured to detect tissue temperaturevalues as well. From local measured tissue temperatures as well as fromthe known temperature of the local perfusate, the user may extrapolateregions of the tissue T having relatively higher temperature values,which may be indicative of tissue having higher perfusion and metabolicactivity (and presumably increased viability). Conversely, regions oftissue with relatively lower temperature values may be indicative oftissue having lower perfusion and metabolic activity (and presumablylowered viability), thus possibly indicating ischemic and/or infarctedtissue regions. The temperature measurements may also be processed 162for visual representation 164, as illustrated by the temperature profile174 as measured by probe 170.

FIG. 13 illustrates a perspective view of a variation of hood 12 havingone or more sensor probes 180 which are located circumferentially aboutthe periphery of hood 12. Several sensor probes 180 may be uniformly (ornon-uniformly) placed around the hood 12 circumference such that whenhood 12 contacts the tissue region T to be inspected, multiplemeasurements or a greater region of the tissue may be interrogated. Eachof the sensor probes 180 may be configured for measuring PO2/PCO2 and/ortemperature as well. Moreover, the measured data may be processed 162 togenerate a concentration profile 182 and/or temperature profile 184, asabove.

The sensor probe(s) in FIG. 12 and/or FIG. 13 may also be configured todetect other tissue parameters besides concentration and temperature.For instance, yet another variation includes utilizing the sensor probesfor detecting the presence of certain biomarkers which are typicallyindicative of tissue injury, and presumably the presence of ischemicand/or infarcted tissue. In such a variation, one or more biochemicalsensor probe(s) may be utilized to measure the presence of certainchemical substances. Typically, damaged tissues release unique chemicalsubstances. In the case of myocardial tissue, damaged cardiac musclesrelease troponin T, I, and C; creatine phosphokinase; MB fraction(CKMB); myoglobin; and lactate dehydrogenase (LDH). By quantitativelymeasuring the concentrations of one or more of these biochemicalmarkers, processor 162 may be used to map the location and degree ofinjury within the tissue.

In yet another variation of FIG. 12 and/or FIG. 13, sensor probe(s) maybe configured to measure electrical current in the interrogated tissueregion T. The pathologic physiologic changes induced by ischemia andinfarction may be evident in the current level measured within injuredtissue. For example, several weeks after myocardial tissue experiencesinfarction, the cardiac muscle undergoes liquefactive necrosis,remodeling, and ultimately scar formation. Scar tissue, comprisedprimarily of fibroblasts and collagen, demonstrates diminishedelectrical conductivity secondary to increased impedance (relative tohealthy myocardium). By electrically sampling levels of tissue impedanceat several points across the region of interest, one may generate a mapdelineating regions of tissue ischemia, infarct in evolution, acuteinfarct, subacute infarct, and old infarct (scar).

In another variation of FIG. 12 and/or FIG. 13, sensor probe(s) may beconfigured to measure electrical potential differences in theinterrogated tissue region T. As such, one or more electrical probe(s)or electrodes may be utilized for measurement of electrical potentialdifference. The presence of pathologic physiologic changes induced byischeinia and/or infarction may be evidenced in the voltages measured,e.g., via an electrocardiogram (ECG) within injured tissues. An ECG is agraphical representation of cardiac electrical activity depictingvoltage (ordinate) as a function of time (abcissa). ECG measurementshave long been utilized to diagnose cardiac pathology including ischemia(S-T segment elevation) and infarction (S-T segment depression, Qwaves). Presumably, intracardiac voltage measurements may demonstratefindings correlating to traditional transcutaneous ECG data. By mappingvoltage differences throughout the tissue of interest, one may generatea map delineating regions of tissue ischernia, acute infarct, subacuteinfarct, and old infarct.

In yet another variation of FIG. 12 and/or FIG. 13, sensor probe(s) maybe configured to detect tissue hardness and deflection differences inthe interrogated tissue region T. As such, one or more probe(s) may beconfigured as pressure-sensitive probes for measuring hardness (e.g.,Rockwell, Vickers, durometer type, etc.) or force required to produce agiven deflection in the tissue of interest. Several weeks afterinfarction, myocardial tissue becomes weakened secondary to coagulativenecrosis. In fact, the patient may be at risk for ventricular rupture.After several more weeks, the necrotic tissue is replaced withfibroblasts (scar tissue) which, although non-contractile, providesrelatively stable structural support for the moving ventricle. It istheorized that the complete but unscarred infarct may demonstrateincreased compliance and decreased hardness relative to normalmyocardial tissue. Similarly, the healed (scarred) old infarct isthought to demonstrate decreased compliance and increased hardnessrelative to normal myocardial tissue. By acquiring multiple measurementsfrom the tissue surface of interest, a map delineating the hardness andextrapolated infarct ages and locations may be generated.

Once a region of ischemic and/or infarcted tissue has been identifiedusing any of the modalities described above, the injured tissue may berepaired or improved, in one variation, by administering one or morebioactive substances into the affected tissue. One method for treatingthe injured tissue may utilize a hollow needle, such as piercing needle160 shown above in FIG. 11A, advanced into the tissue through hood 12while under direct visualization. Another variation may utilize helicaldelivery needle 190, as shown in the perspective view of FIG. 14A. Ahollow helical delivery needle 190 may be positioned upon elongatemember 192 and it may also define a plurality of openings 194 along itssurface through which one or more bioactive substances may be infused.In use, as shown in the perspective view of FIG. 14B, once the tissueregion T of interest is identified, the helical delivery needle 190 maybe gently twisted and advanced into the tissue. Once partially or fullyembedded, bioactive chemicals may be infused within the tissue via theopenings 194 in the needle 190. In another variation, rather thanutilizing a single helical delivery needle, multiple delivery needles190 may be positioned to extend along support struts/elongate members200 along hood 12 and extend distally past the hood 12 for advancementinto the underlying tissue, as shown in the perspective view of FIG. 15.

In yet another alternative for treating tissue regions identified aspotentially ischemic and/or infarcted, a laser catheter may be utilizedwhile under direct visualization of the tissue region of interest. FIGS.16A and 16B illustrate perspective views where a laser probe or fiber210, e.g., an optical fiber bundle coupled to a laser generator, may beinserted through the work channel of the tissue visualization catheter.When actuated, laser energy 212 may be channeled through probe 210 andapplied to the underlying tissue at different angles to form a varietyof lesion patterns. Further examples of laser or ablation probes aredescribed in detail in U.S. patent application Ser. No. 11/775,819 filedJul. 10, 2007, which is incorporated herein by reference in itsentirety.

As the laser energy 212 is highly focused with intense energy toprecisely ablate small quantities of tissue, the laser probe 210 may beused to perforate the tissue surface and/or deeper layers. Variousbioactive chemicals may then be infused through hood 12 or through acatheter and directly into the tissue via the perforations.Alternatively, the tissue may be perforated during or after the variousbioactive chemicals have been infused into the tissue. In yet anotheralternative, the tissue may be simply revascularized with the lasertreatment and the infusion of bioactive chemicals may be omittedentirely, if so desired.

In yet another variation, a bioactive substance may be implanted into ornear the injured tissue region. As shown in the partial cross-sectionalview of the heart H, a bioactive substance 220 may be delivered anddeposited directly into the tissue wall, e.g., in the anterolateralmyocardium of the left ventricle, as shown in FIG. 17. The bioactivesubstance 220 may be delivered utilizing any number of delivery devicesthrough hood 12 while under direct visualization, e.g., via a needle asdescribed above. As shown, the deposited administration of a bioactivesubstance 220 within the tissue of interest may or may not beencapsulated for controlled release over time.

In treating the tissue with bioactive substances, any number of suitablematerials may be delivered utilizing the devices and methods herein. Forinstance, bioactive substances for healing and/or regeneratingfunctional tissue may include the use of stem cells, which are proteancells from which other specialized cell lines are formed. Most damagedtissues undergo a natural process of death, resorption, and scarformation. If the stem cells, e.g., from a patient's bone marrow, can beidentified and isolated these may be transplanted into the damagedtissue of interest. Ideally, the specific stem cell line responsible forgenerating the tissue of interest is identified and transplanted.Preclinical studies have established that implantation of bone marrowmononuclear into ischemic limbs increased collateral vessel formation.Direct myocardial injection of, e.g., bone marrow cells, into theinfarct border zone produced improved LV function and infarct tissueperfusion (Tse, et al. Lancet 2003, Jan. 4; 361 (9357): 47-9), which isincorporated herein by reference in its entirety. It follows that byutilizing any of the previously described devices for directvisualization to identify the location of damaged tissue (e.g. infractedmyocardium) and any of the delivery systems to deposit the bioactivesubstances, one may deliver bone marrow cells (e.g. vascular progenitorcells) to stimulate angiogenesis for improved tissue perfusion andfunction as well as new intrinsic tissue formation (e.g. myogenesis).

Another example of a bioactive substance which may be infused into theidentified injured tissue may include biologic substances which promoteangiogenesis and subsequently improve local tissue perfusion andfunction. Vascular endothelial growth factor (VEGF) is an angiogenicfactor regulating vascular endothelial cell migration, proliferation,and permeability. Fibroblast growth factor (FGF) induces microvascularendothelial cell growth and neovascularization. Similarly,pro-angiogenic cytokines including tumor necrosis factor alpha (TNF) andinterleukin 8 (IL8), as well as the peptides SIKVAV (derived fromlaminin 1) and neuropeptide Y (NPY) have been shown to demonstratesimilar effects.

Aside from administering bioactive agents, chemical irritants may alsobe delivered to tissue utilizing any of the methods and systemsdescribed herein to promote angiogenesis and improved tissue perfusionand function.

The applications of the disclosed invention discussed above are notlimited to certain treatments or regions of the body, but may includeany number of other treatments and areas of the body. Modification ofthe above-described methods and devices for carrying out the invention,and variations of aspects of the invention that are obvious to those ofskill in the arts are intended to be within the scope of thisdisclosure. Moreover, various combinations of aspects between examplesare also contemplated and are considered to be within the scope of thisdisclosure as well.

1. (canceled)
 2. A method comprising: steering a deployment catheter tolocate a distal end of the deployment catheter at a position within apatient anatomy; articulating a delivery catheter extending through andfrom the distal end of the deployment catheter while the distal end ofthe deployment remains at the position; and deploying an instrumentthrough the delivery catheter.
 3. The method of claim 2 wherein thedelivery catheter includes an optical imaging assembly.
 4. The method ofclaim 2 further comprising: extending a tissue piercing device from thedelivery catheter.
 5. The method of claim 2 wherein the deploymentcatheter is steered under computer control.
 6. The method of claim 2further comprising: conducting a first procedure with the instrumentwhile the distal end of the delivery catheter is articulated in a firstdirection and the distal end of the deployment catheter is at theposition within the patient anatomy; and conducting a second procedurewith the instrument while the distal end of the delivery catheter isarticulated in a second direction and the distal end of the deploymentcatheter is at the position within the patient anatomy.
 7. The method ofclaim 2 further comprising: capturing a first image while the distal endof the delivery catheter is articulated in a first direction and thedistal end of the deployment catheter is at the position within thepatient anatomy; and capturing a second image while the distal end ofthe delivery catheter is articulated in a second direction and thedistal end of the deployment catheter is at the position within thepatient anatomy.
 8. The method of claim 2 further comprising:articulating a sheath through which the deployment catheter extends,wherein articulation of the sheath is separate from the steering of thedeployment catheter.
 9. The method of claim 8 further comprising:translating the deployment catheter independently of the sheath.
 10. Themethod of claim 8 wherein articulating the sheath includes manipulatingat least one wire extending within the sheath.
 11. The method of claim 2further comprising delivering a fluid through a fluid delivery lumen ofthe delivery catheter.
 12. The method of claim 2 wherein steering thedeployment catheter includes manipulating at least one wire extendingwithin the deployment catheter.
 13. The method of claim 2 whereinarticulating the delivery catheter includes manipulating at least onewire extending within the delivery catheter.
 14. The method of claim 2wherein the instrument is an ablation probe.
 15. The method of claim 2further comprising stabilizing the deployment catheter at the positionwithin the patient anatomy.
 16. The method of claim 2 wherein thedelivery catheter includes an optical fiber.